The adrenal glands are two secretory organs located on top of the kidneys. Each gland consists of two parts, the cortex and the medulla, which have independent functions. The adrenal cortex secretes numerous steroids, e.g. corticoids and androgens. These steroids are involved in various metabolic processes throughout the body and are essential for homeostasis, the maintenance of the internal environment of the body. For example, glucocorticoids such as cortisol, play a role in carbohydrate and protein metabolism, while mineralocorticoids, such as aldosterone, function in electrolyte and water metabolism. The androgens supplement the hormones secreted by the gonads.
Defects in adrenal cortical function result in severe metabolic disturbances that affect the entire body. If the adrenals were removed, the subject would die within a short period, unless appropriate medications were administered. Some tumors, either benign or cancerous, in one or both of the adrenal glands cause increased androgen synthesis. The result is masculinization, independent of the sex or age of the affected patient. Other tumors cause selective increases in glucocorticoid synthesis or in mineralocorticoid synthesis, resulting in accumulation of fat, hyperglycemia, muscle weakness, and decreased immunity to infection, as well as other symptoms.
Typical therapy is aimed at removal or destruction of the hyperfunctioning tissue. For this reason, it is necessary to identify and localize the malfunction in one or both of the adrenal glands. Of special interest is the diagnosis of these disorders using non-invasive techniques. Heretofore, extracorporeal imaging of the adrenal glands has been attempted using radiolabelled cholesterol and radiolabelled cholesterol derivatives as probes.
These probes were chosen because cholesterol is a principal precursor in steroid biosynthesis. While steroids can be synthesized de novo in the adrenal glands from a simple two-carbon acetate precursor, it is believed that the majority of steroids may be synthesized instead from cholesterol derived from low density lipoproteins which circulate in the blood stream.
Beierwaltes and his colleagues used .sup.131 I-iodocholesterol and other iodinated cholesterol-like compounds to visualize adrenal uptake in animals by extracorporeal imaging (Beierwaltes et al., Seminars in Nuclear Medicine VIII: 5, 1978; and Blair et al., Journal of Nuclear Medicine 12: 176, 1971). In experiments in animals, these researchers found that, shortly after injection, uptake of cholesterol was relatively uniform throughout all tissues, but that after one or two days, cholesterol was retained to a greater extent in the adrenal glands. However, their attempts to image the human adrenal were not as successful. They reported evidence of imaging of the human adrenal glands using a radiolabelled iodocholesterol derivative only at 5-7 days after injection.
Shapiro et al. have also investigated the usefulness of extracorporeal imaging with .sup.75 Se-selenomethylcholesterol for studying human adrenal pathologies (Clinical Endocrinology 15: 19, 1981). Using this radiolabelled cholesterol probe, they found that the adrenal gland could be imaged. They also found that this probe could be used to diagnose some, but not all adrenal pathologies.
While Shapiro's probe permits imaging of the human adrenal glands, it requires seven to ten days after injection of the probe before the cholesterol concentrates in the adrenal glands to a sufficient extent for the glands to be visualized by extracorporeal imaging. This lengthy time delay increases the radioactive dose required to provide a suitable image, and therefore interferes with its effectiveness as an experimental and clinical diagnostic tool.
Thus both Beierwaltes' and Shapiro's methods described above demonstrate the limitations of radiolabelled cholesterol for use as an adrenal imaging agent. An ideal imaging agent would quickly concentrate in the adrenal glands relative to other organs, and would therefore permit imaging of the adrenals shortly after injection of the radiolabelled imaging agent. It would also expose the subject to a minimal radioactive dose.